A therapeutic antibody is an agent which comprises an antibody as an active ingredient. An antibody has the property to specifically bind to a specific molecule (antigen) (Non-patent Reference 1).
The therapeutic antibody is useful in treating cancer patients. Currently, an anti-HER 2 antibody Trastuzumab (Herceptin: registered trademark), an anti-EGFR antibody Cetuximab (Erbitux: registered trademark) (Non-patent Reference 1), and the like are on the market.
When a therapeutic antibody is administered to a patient, expression of an antigen on cancer cells is analyzed before administration of the anti-cancer antibody. For the therapeutic antibody to show its effect, it is necessary that the antibody molecule binds to the antigen of cancer cells (Non-patent Reference 1). Accordingly, there are carried out by selecting a patient in which expression of antigen on cancer cells is observed screening, and the therapeutic antibody is administered to the selected patients (Non-patent Reference 2). As a specific example, Hercep Test (registered trademark) before administration of Trastuzumab can be cited. In the Hercep Test, a kit for testing expression of HER 2 as the antigen of Trastuzumab is used, and expression level of HER 2 in a cancer tissue of a patient is measured by an immunohistological staining method (Non-patent. Reference 2). Trastuzumab is administered only to the patient whose expression of HER 2 was found by the Hercep Test (Non-patent Reference 3).
Screening of a patient to be administered with the therapeutic antibody is important from the viewpoint of side effects. In addition, the therapeutic antibody should not be administered to patientsnot predicting in its effectiveness. Cardiac toxicity has been reported as a side effect of Trastuzumab (Non-patent Reference 4), and pimple-like skin erythema or the like has been reported as a side effect of Cetuximab (Non-patent Reference 5).
However, even if a patient is screened based on the presence or absence of the antigen expression, the therapeutic antibody is not necessarily effective in all patients. It has been reported that the objective response rate of Herceptin was 36% in a second phase clinical test carded out on the HER 2 high expression breast cancer patients screened by Hercep Test (Non-patent Reference 6).
E-cadherin is localized on the surface cell membrane, and is involved in the formation and maintenance of cell adhesion (Non-patent Reference 7). E-cadherin does not function by the E-cadherin alone but functions by co-operating with certain molecules (Non-patent Reference 7). Catenin connects E-cadherin with cytoskeleton by binding to the intracellular domain of E-cadherin (Non-patent Reference 7).
Deletion of E-cadherin function is known in cancer patients. As the deletion of E-cadherin function, a case in which the expression level of E-cadherin protein is decreased, a case in which the expression level of a molecule which cooperates with E-cadherin protein is decreased, and the like are known (Non-patent Reference 8). It is known that deletion of expression of E-cadherin protein was found in 14% of gastric cancer patients and, in addition, E-cadherin was not localized on the cell membrane in 48% of patients among the patients in which expression of E-cadherin was found (Non-patent Reference 9).
It has been reported that there is a relation between deletion of E-cadherin function and prognosis of patients (Non-patent Reference 10). For example, there is a report stating that, among prostatic cancer patients to whom radiotherapy or hormone therapy was applied, patients who have low expression level of E-cadherin protein are poor in prognosis in comparison with the patients having normal expression level of E-cadherin protein (Non-patent Reference 10).
It has been reported that survival effect of anti-HLA antibody is enhanced in a mouse model to which a human colon cancer cell line was transplanted, as a result of the neutralization of cadherin function due to administration of an anti-cadherin antibody (Non-patent Reference 11). A possibility was suggested in this report that a medicament which neutralizes cadherin function is useful as an agent for enhancing the effect of therapeutic antibody (Non-patent Reference 11).
However, it is not known that a patient to whom anti-cancer therapeutic antibody is effective can be screened by examining conditions of the original cadherin function in cancer cells.    Non-patent Reference 1: Nature Reviews Cancer 2006; 6: 714-27    Non-patent Reference 2: European Journal of Cancer 2000; 36: 170-6    Non-patent Reference 3: Clinical Cancer Research 2001; 7: 1669-75    Non-patent Reference 4: British Journal of Cancer 2006; 94: 1016-20    Non-patent Reference 5: Journal of Clinical Oncology 2004; 22: 1201-8    Non-patent Reference 6 Journal of Clinical Oncology 2005; 23: 2162-71    Non-patent Reference 7: Molecular Cell Biology Research Communications 1999; 2: 77-85    Non-patent Reference 8: Cancer and Metastasis Review 1999; 18: 15-30    Non-patent Reference 9: Annals of Surgery 2005; 242: 676-83    Non-patent Reference 10: Cancer Reseach 1994; 54: 3929-33    Non-patent Reference 11: Cancer Reseach 2002; 62: 6891-900